Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen

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ID: 116388
2010
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Abstract
The ability of the thymus to generate a population of T cells that is, for the most part, self-restricted and self-tolerant depends to a great extent on the Ags encountered during differentiation. We recently showed that mycobacteria disseminate to the thymus, which raised the questions of how mycobacteria within the thymus influence T cell differentiation and whether such an effect impacts host–pathogen interactions. Athymic nude mice were reconstituted with thymic grafts from Mycobacterium avium -infected or control noninfected donors. T cells generated from thymi of infected donors seemed generally normal, because they retained the ability to reconstitute the periphery and to respond to unspecific stimuli in vitro as well as to antigenic stimulation with third-party Ags, such as OVA, upon in vivo immunization. However, these cells were unable to mount a protective immune response against a challenge with M. avium . The observation that thymic infection interferes with T cell differentiation, generating T cells that are tolerant to pathogen-specific Ags, is of relevance to understand the immune response during chronic persistent infections. In addition, it has potential implications for the repertoire of T cells generated in patients with a mycobacterial infection recovering from severe lymphopenia, such as patients coinfected with HIV and receiving antiretroviral therapy.
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nobrega2010thedissemination Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Claudia Nobrega;Susana Roque;Cláudio Nunes-Alves;Angela Coelho;Irene Medeiros;António Gil Castro;Rui Appelberg;Margarida Correia-Neves;Claudia Nobrega;Susana Roque;Cláudio Nunes-Alves;Angela Coelho;Irene Medeiros;António Gil Castro;Rui Appelberg;Margarida Correia-Neves;
Journal the journal of immunology
Year 2010
DOI
10.4049/jimmunol.0902152
URL
https://dx.doi.org/10.4049%2Fjimmunol.0902152
Keywords
image processing National Center for Biotechnology Information NCBI NLM MEDLINE Mice animals pubmed abstract nih national institutes of health national library of medicine research support non-u.s. gov't female fluorescent antibody technique nude computer-assisted flow cytometry t-lymphocytes / immunology* immune tolerance / immunology* tuberculosis / immunology* pmid:19949112 doi:10.4049/jimmunol.0902152 claudia nobrega susana roque margarida correia-neves cell differentiation / immunology mycobacterium avium / immunology t-lymphocytes / cytology thymus gland / immunology thymus gland / microbiology* tuberculosis / veterinary

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